Point-of-care COVID-19 assays that are more sensitive than the current RT-PCR (reverse transcription polymerase chain reaction) gold standard assay are needed to improve disease control efforts. We describe the development of a portable, ultrasensitive saliva-based COVID-19 assay with a 15-min sample-to-answer time that does not require RNA isolation or laboratory equipment. https://www.selleckchem.com/products/i-bet-762.html This assay uses CRISPR-Cas12a activity to enhance viral amplicon signal, which is stimulated by the laser diode of a smartphone-based fluorescence microscope device. This device robustly quantified viral load over a broad linear range (1 to 105 copies/μl) and exhibited a limit of detection (0.38 copies/μl) below that of the RT-PCR reference assay. CRISPR-read SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) RNA levels were similar in patient saliva and nasal swabs, and viral loads measured by RT-PCR and the smartphone-read CRISPR assay demonstrated good correlation, supporting the potential use of this portable assay for saliva-based point-of-care COVID-19 diagnosis.Health systems face major challenges during the COVID-19 pandemic with new information and challenges emerging daily and frequently changing guidelines. Online forward triage tools (OFTTs) provide useful information, direct patients and free physician resources.We implemented an OFTT targeted at the current pandemic, adapted the content and goals and assessed its effects. The OFTT was implemented on 2 March 2020 and modified regularly based on the revised testing criteria issued by the Swiss Federal Office of Public Health. After testing criteria liberalised, a chatbot tool was set up on 9 April 2020 to assess urgency of testing, referral to available testing sites and need for emergency care.In the first 40 days of the OFTT, there were more than 17?300 visitors and 69.8% indicated they would have contacted the healthcare system if the online test had not been available. During the initial week of operation, using the conservative testing strategy, 9.1% of visitors received recommendations to be tested, which increased to 36.0% of visitors after a change in testing criteria on 9 March 2020. Overall, since the implementation of the tool, 26.27% of all users of the site have been directed to obtain testing. The Chatbot tool has had approximately 50 consults/day.Setting up an OFTT should be considered as part of local strategies to cope with the COVID-19 pandemic. It may ease the burden on the healthcare system, reassure patients and inform authorities. To account for the dynamic development of the pandemic, frequent adaptation of the tool is of great importance. Further research on clinical outcomes of OFTT is urgently needed.Nearly 110 susceptibility loci for rheumatoid arthritis (RA) with modest effect sizes have been identified by population-based genetic association studies, suggesting a large number of undiscovered variants behind a highly polygenic genetic architecture of RA. Here, we performed the largest-ever trans-ancestral meta-analysis with the aim to identify new RA loci and to better understand RA biology underlying genetic associations.
Genome-wide RA association summary statistics in three large case-control collections consisting of 311 292 individuals of Korean, Japanese and European populations were used in an inverse-variance-weighted fixed-effects meta-analysis. Several computational analyses using public omics resources were conducted to prioritise causal variants and genes, RA variant-implicating features (tissues, pathways and transcription factors) and potentially repurposable drugs for RA treatment.
We identified 11 new RA susceptibility loci that explained 6.9% and 1.8% of the single-nucleotide polymorphism-based heritability in East Asians and Europeans, respectively, and confirmed 71 known non-human leukocyte antigens (HLA) susceptibility loci, identifying 90 independent association signals. The RA variants were preferentially located in binding sites of various transcription factors and in cell type-specific transcription-activation histone marks that simultaneously highlighted the importance of CD4T-cell activation and the potential role of non-immune organs in RA pathogenesis. A total of 615 plausible effector genes, based on gene-based associations, expression-associated variants and chromatin interaction, included targets of drugs approved for RA treatments and potentially repurposable drugs approved for other indications.
Our findings provide useful insights regarding RA genetic aetiology and variant-driven RA pathogenesis.
Our findings provide useful insights regarding RA genetic aetiology and variant-driven RA pathogenesis.Patients with rheumatoid arthritis (RA) commonly use oral glucocorticoids (GCs) and proton pump inhibitors (PPIs), both associated with osteoporotic fractures. We investigated the association between concomitant use of oral GCs and PPIs and the risk of osteoporotic fractures among patients with RA.
This was a cohort study including patients with RA aged 50+ years from?the Clinical Practice Research Datalink between 1997 and 2017. Exposure to oral GCs and PPIs was stratified by the most recent prescription as current use (&lt;6 months), recent use (7-12 months) and past use (&gt;1?year); average daily and cumulative dose; and duration of use. The risk of incident osteoporotic fractures (including hip, vertebrae, humerus, forearm, pelvis and ribs) was estimated by time-dependent Cox proportional-hazards models, statistically adjusted for lifestyle parameters, comorbidities and comedications.
Among 12?351 patients with RA (mean age of 68 years, 69% women), 1411 osteoporotic fractures occurred. Concomitant current use of oral GCs and PPIs was associated with a 1.6-fold increased risk of osteoporotic fractures compared with non-use (adjusted HR 1.60, 95%?CI 1.35 to 1.89). This was statistically different from a 1.2-fold increased osteoporotic fracture risk associated with oral GC or PPI use alone. Most individual fracture sites were significantly associated with concomitant use of oral GCs and PPIs. Among concomitant users, fracture risk did not increase with higher daily dose or duration of PPI use.
There was an interaction in the risk of osteoporotic fractures with concomitant use of oral GCs and PPIs. Fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs.
There was an interaction in the risk of osteoporotic fractures with concomitant use of oral GCs and PPIs. Fracture risk assessment could be considered when a patient with RA is co-prescribed oral GCs and PPIs.